2023年12月，中国科学院分子细胞科学研究中心；中国科学院上海生物化学与细胞生物学研究所；中国科学院RNA科学与工程重点实验室；武汉大学生命科学学院；太康生命与医学科学中心；RNA研究所；湖北省细胞稳态重点实验室；中国科学院分析化学分离科学重点实验室；武汉中国科学院大连化学物理研究所国家色谱研究中心；中国科学院大学杭州高等研究院生命科学学院浙江省系统健康科学重点实验室(Key Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China；College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, China；CAS Key Laboratory of Separation Sciences for Analytical Chemistry,  National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China；Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences,Hangzhou, China) Jing Fan老师研究团队在《The EMBO Journal》上发表论文：

“CDK11 requires a critical activator SAP30BP to regulate pre-mRNA splicing”

“CDK11需要一个关键的激活子SAP30BP来调节pre-mRNA剪接”

Abstract：

CDK11 is an emerging druggable target for cancer therapy due to its prevalent roles in phosphorylating critical transcription and splicing factors and in facilitating cell cycle progression in cancer cells. Like other cyclin-dependent kinases, CDK11 requires its cognate cyclin, cyclin L1 or cyclin L2, for activation. However, little is known about how CDK11 activities might be modulated by other regulators. In this study, we show that CDK11 forms a tight complex with cyclins L1/L2 and SAP30BP, the latter of which is a poorly characterized factor. Acute degradation of SAP30BP mirrors that of CDK11 in causing widespread and strong defects in pre-mRNA splicing. Furthermore, we demonstrate that SAP30BP facilitates CDK11 kinase activities in vitro and in vivo, through ensuring the stabilities and the assembly of cyclins L1/L2 with CDK11. Together, these findings uncover SAP30BP as a critical CDK11 activator that regulates global pre-mRNA splicing.

摘要：

CDK11是一个新兴的癌症治疗药物靶点，因为它在磷酸化关键转录和剪接因子以及促进癌细胞细胞周期进程中发挥着普遍作用。像其他细胞周期蛋白依赖性激酶一样，CDK11需要其同源细胞周期蛋白，细胞周期蛋白L1或细胞周期蛋白L2来激活。然而，对于CDK11的活性如何被其他调节因子调节，研究人员所知甚少。在这项研究中，研究人员发现CDK11与细胞周期蛋白L1/L2和SAP30BP形成紧密复合物，后者是一个特征不明显的因子。SAP30BP的急性降解与CDK11一样，在pre-mRNA剪接中引起广泛而强烈的缺陷。此外，研究人员证明SAP30BP通过确保细胞周期蛋白L1/L2与CDK11的稳定性和组装，促进了CDK11激酶在体外和体内的活性。综上所述，这些发现揭示了SAP30BP作为一个关键的CDK11激活因子，调控全局pre-mRNA剪接。

该论文中，HeLa和 HAP1细胞的体外培养是使用Ausbian特级胎牛血清完成的。